tbuckley/cabot-search huggingface dataset:
Mutated HRAS Activates YAP1–AXL Signaling to Drive Metastasis of Head and Neck Cancer
Authors: Sankar Jagadeeshan, Manu Prasad, Mai Badarni, Talal Ben-Lulu, Vijayasteltar Belsamma Liju, Sooraj Mathukkada, Claire Saunders, Avital Beeri Shnerb, Jonathan Zorea, Ksenia M. Yegodayev, Monica Wainer, Liza Vtorov, Irit Allon, Ofir Cohen, Gro Gausdal, Dinorah Friedmann-Morvinski, Sok Ching Cheong, Alan L. Ho, Ari J. Rosenberg, Linda Kessler, Francis Burrows, Dexin Kong, Jennifer R. Grandis, J. Silvio Gutkind, Moshe Elkabets
Journal: Cancer Research (2023)

The survival rate for patients with head and neck cancer (HNC) diagnosed with cervical lymph node (cLN) or distant metastasis is low. Genomic alterations in the HRAS oncogene are associated with advanced tumor stage and metastasis in HNC. Elucidation of the molecular mechanisms by which mutated HRAS (HRASmut) facilitates HNC metastasis could lead to improved treatment options for patients. Here, we examined metastasis driven by mutant HRAS in vitro and in vivo using HRASmut human HNC cell lines, patient-derived xenografts, and a novel HRASmut syngeneic model. Genetic and pharmacological manipulations indicated that HRASmut was sufficient to drive invasion in vitro and metastasis in vivo. Targeted proteomic analysis showed that HRASmut promoted AXL expression via suppressing the Hippo pathway and stabilizing YAP1 activity. Pharmacological blockade of HRAS signaling with the farnesyltransferase inhibitor tipifarnib activated the Hippo pathway and reduced the nuclear export of YAP1, thus suppressing YAP1-mediated AXL expression and metastasis. AXL was required for HRASmut cells to migrate and invade in vitro and to form regional cLN and lung metastases in vivo. In addition, AXL-depleted HRASmut tumors displayed reduced lymphatic and vascular angiogenesis in the primary tumor. Tipifarnib treatment also regulated AXL expression and attenuated VEGFA and VEGFC expression, thus regulating tumor-induced vascular formation and metastasis. Our results indicate that YAP1 and AXL are crucial factors for HRASmut-induced metastasis and that tipifarnib treatment can limit the metastasis of HNC tumors with HRAS mutations by enhancing YAP1 cytoplasmic sequestration and downregulating AXL expression.Mutant HRAS drives metastasis of head and neck cancer by switching off the Hippo pathway to activate the YAP1-AXL axis and to stimulate lymphovascular angiogenesis.
Tafamidis Treatment Decreases 99mTc-Pyrophosphate Uptake in Patients With Hereditary Ala97Ser Transthyretin Amyloid Cardiomyopathy
Authors: An-Li Yu, Yi-Chieh Chen, Cheng-Hsuan Tsai, Chi-Chao Chao, Mao-Yuan Su, Jimmy Jyh-Ming Juang, Ming-Jen Lee, Sung-Tsang Hsieh, Mei-Fang Cheng, Yen-Hung Lin
Journal: JACC. Cardiovascular imaging (2023)
Lobar or Sublobar Resection for Peripheral Stage IA Non–Small-Cell Lung Cancer
Authors: Nasser Altorki, Xiaofei Wang, David Kozono, Colleen Watt, Rodney Landrenau, Dennis Wigle, Jeffrey Port, David R. Jones, Massimo Conti, Ahmad S. Ashrafi, Moishe Liberman, Kazuhiro Yasufuku, Stephen Yang, John D. Mitchell, Harvey Pass, Robert Keenan, Thomas Bauer, Daniel Miller, Leslie J. Kohman, Thomas E. Stinchcombe, Everett Vokes
Journal: New England Journal of Medicine (2023)

The increased detection of small-sized peripheral non–small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy.
More on Myocarditis after BNT162b2 Vaccination in Israeli Adolescents
Authors: Marcos R Tovani-Palone, Shankargouda Patil
Journal: New England Journal of Medicine (2023)

To the Editor: In their letter, Witberg et al. (Nov.10 issue) 1 describe cases of myocarditis that were diagnosed among Israeli adolescents after BNT162b2 vaccination.The findings of this study are of great relevance to the scientific community, governments, policymakers, and stakeholders.However, after a reflective and thorough reading, we came across a possible limitation of the study, which has the potential to influence the results.The authors do not mention whether the study participants had been previously tested for Covid-19.If such testing had not been performed, a considerable number of the participants may have been infected but were asymptomatic at the time of vaccination, resulting in cases of myocarditis that emerged during the symptomatic phase of Covid-19 rather than as adverse effects of the vaccine.However, we believe that the authors' findings serve as an important basis for further investigation in this field.
Initiating the Era of “Precision” Lung Cancer Surgery
Authors: Valerie W. Rusch
Journal: New England Journal of Medicine (2023)

Surgical resection for lung cancer dates to the early 20th century. Evarts Graham is credited with performing the first successful pneumonectomy in 1933 for what was then an uncommon disease. During the next 25 years, surgeons focused on improving outcomes through better resection techniques. In 1962, retrospective data suggested that lobectomy for early-stage non–small-cell lung cancer (NSCLC) yielded a 5-year overall survival similar to that reported after pneumonectomy,1 and lobectomy gradually became the more commonly performed operation. By the 1980s, advances in imaging (e.g., computed tomography [CT]), staging by means of mediastinoscopy, and routine intraoperative lymphadenectomy enabled the identification of . . .
Phase 2 Trial of Difelikefalin in Notalgia Paresthetica
Authors: Brian S. Kim, Robert Bissonnette, Kristine Nograles, Catherine Munera, Nilam Shah, Alia Jebara, Joshua Cirulli, Joana Goncalves, Mark Lebwohl
Journal: New England Journal of Medicine (2023)

Notalgia paresthetica is a neuropathic disorder characterized by pruritus in a circumscribed region of the upper back. Difelikefalin, a selective kappa opioid receptor agonist, has shown efficacy in other chronic pruritic conditions and is being investigated for the treatment of notalgia paresthetica.
Early Treatment with Pegylated Interferon Lambda for Covid-19
Authors: Gilmar Reis, Eduardo A.S. Moreira Silva, Daniela C. Medeiros Silva, Lehana Thabane, Vitoria H.S. Campos, Thiago S. Ferreira, Castilho V.Q. Santos, Ana M.R. Nogueira, Ana P.F.G. Almeida, Leonardo C.M. Savassi, Adhemar D. Figueiredo-Neto, Ana C.F. Dias, Adelino M. Freire Júnior, Carina Bitarães, Aline C. Milagres, Eduardo D. Callegari, Maria I.C. Simplicio, Luciene B. Ribeiro, Rosemary Oliveira, Ofir Harari, Lindsay A. Wilson, Jamie I. Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Christina M. Guo, Eve H. Limbrick-Oldfield, Steve Kanters, Gordon H. Guyatt, Craig R. Rayner, Christopher Kandel, Mia J. Biondi, Robert Kozak, Bettina Hansen, M. Atif Zahoor, Paul Arora, Colin Hislop, Ingrid Choong, Jordan J. Feld, Edward J. Mills, Jeffrey S. Glenn
Journal: New England Journal of Medicine (2023)

The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear.
The Association Between Obstructive Sleep Apnea and Abnormal 82Rubidium Cardiac PET Perfusion Myocardial Flow Reserve
Authors: Ehimen C. Aneni, Stephanie L. Thorn, Attila Feher, Jia Hong Chen, Albert J. Sinusas, H. Klar Yaggi, Edward J. Miller
Journal: JACC. Cardiovascular imaging (2023)
Case 4-2023: A 56-Year-Old Man with Abnormal Results on Liver Testing
Authors: Irun Bhan, Esperance A. Schaefer, William R. Bradley, Josanna M. Rodriguez-Lopez, Jerome C. Crowley, Bailey Hutchison
Journal: New England Journal of Medicine (2023)

A 56-year-old man was evaluated for abnormal results on liver testing. He had a history of alcohol and opioid use. Imaging revealed a nodular hepatic contour. Additional diagnostic tests were performed.
Darolutamide Maintenance in Patients With Metastatic Castration-Resistant Prostate Cancer With Nonprogressive Disease After Taxane Treatment (SAKK 08/16)
Authors: Silke Gillessen, Giuseppe Procopio, Stefanie Hayoz, Eloïse Kremer, Michael Schwitter, Orazio Caffo, David Lorente, Augusto Pedrazzini, Guilhem Roubaud, Soazig Nenan, Aurelius Omlin, Consuelo Buttigliero, Juan Ignacio Delgado Mingorance, Aránzazu González-del-Alba, Maria Teresa Delgado, Franco Nole, Fabio Turco, Ricardo Pereira Mestre, Karin Ribi, Richard Cathomas
Journal: Journal of Clinical Oncology (2023)

PURPOSE To assess the efficacy and safety of darolutamide maintenance after successful taxane chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS Swiss Group for Clinical Cancer Research (SAKK) 08/16 is a randomized phase II study. Patients with mCRPC who received prior androgen-receptor pathway inhibitors (ARPIs) and subsequently had nonprogressive disease on a taxane were randomly assigned to darolutamide 600 mg twice a day or placebo twice a day. The primary end point was radiographic progression-free survival (rPFS) at 12 weeks. Secondary end points were rPFS, event-free survival, overall survival (OS), prostate-specific antigen (PSA) 50% response rate, and adverse events. RESULTS Overall, 92 patients were recruited by 26 centers. Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior ARPI was abiraterone in 60%, enzalutamide in 31%, and both in 9%. rPFS at 12 weeks was significantly improved with darolutamide (64.7% v 52.2%; P = .127). Median rPFS on darolutamide was 5.5 versus 4.5 months on placebo (hazard ratio [HR], 0.54 [95% CI, 0.32 to 0.91]; P = .017), and median event-free survival was 5.4 versus 2.9 months (HR, 0.46 [95% CI, 0.29 to 0.73]; P = .001). PSA 50% response rate was improved (22% v 4%; P = .014). Median OS for darolutamide was 24 versus 21.3 months for placebo (HR, 0.62 [95% CI, 0.3 to 1.26]; P = .181). Treatment-related adverse events were similar in both arms. CONCLUSION SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI.
Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium
Authors: Yucai Wang, Preetesh Jain, Frederick L. Locke, Matthew J. Maurer, Matthew J. Frank, Javier L. Munoz, Saurabh Dahiya, Amer M. Beitinjaneh, Miriam T. Jacobs, Joseph P. Mcguirk, Julie M. Vose, Andre Goy, Charalambos Andreadis, Brian T. Hill, Kathleen A. Dorritie, Olalekan O. Oluwole, Abhinav Deol, Jonas Paludo, Bijal Shah, Trent Wang, Rahul Banerjee, David B. Miklos, Aaron P. Rapoport, Lazaros Lekakis, Armin Ghobadi, Sattva S. Neelapu, Yi Lin, Michael L. Wang, Michael D. Jain
Journal: Journal of Clinical Oncology (2023)

PURPOSE Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication. PATIENTS AND METHODS Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines. RESULTS Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis. CONCLUSION In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.
Mn<sub>3</sub>O<sub>4</sub> Nanoshell Coated Metal–Organic Frameworks with Microenvironment‐Driven O<sub>2</sub> Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies
Authors: Wenya Li, Rongtian Li, Qiang Ye, Yiming Zou, Xing Lu, Wenhua Zhang, Jinxiang Chen, Yinghua Zhao
Journal: Advanced Healthcare Materials (2023)

Abstract Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple‐negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN‐224 is selected as the carrier to enable effective cancer therapy through light‐activated reactive oxygen species (ROS) formation, and the PCN‐224@Mn 3 O 4 @HA is created in a simple one‐step process by coating Mn 3 O 4 nanoshells on the PCN‐224 template, which can then be used as an “ROS activator” to exert catalase‐ and glutathione peroxidase‐like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN‐224. Meanwhile, Mn 2+ produced cytotoxic hydroxyl radicals (∙OH) via the Fenton‐like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment (TME), Mn 3 O 4 nanoshells downregulated hypoxia‐inducible factor 1 α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light‐controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergistic PDT/CDT, and prevent tumor resurgence by remodeling TME.
Even Mild Concussions Tied to Worse Cognition Later in Life
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
FDA Proposes Individual Risk Assessment for Blood Donation
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Paxlovid Alternative Is Similarly Effective
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Publisher Correction: Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis
Authors: Z. Oaks, A. Patel, N. Huang, G. Choudhary, T. Winans, T. Faludi, D. Krakko, M. Duarte, J. Lewis, M. Beckford, S. Blair, R. Kelly, S. K. Landas, F. A. Middleton, J. M. Asara, S. K. Chung, D. R. Fernandez, K. Banki, A. Perl
Journal: Nature Metabolism (2023)
Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance
Authors: Diego F. Calvisi, Luke Boulter, Javier Vaquero, Anna Saborowski, Luca Fabris, Pedro M. Rodrigues, Cédric Coulouarn, Rui E. Castro, Oreste Segatto, Chiara Raggi, Luc J. W. van der Laan, Guido Carpino, Benjamin Goeppert, Stephanie Roessler, Timothy J. Kendall, Matthias Evert, Ester Gonzalez-Sanchez, Juan W. Valle, Arndt Vogel, John Bridgewater, Mitesh J. Borad, Gregory J. Gores, Lewis R. Roberts, Jose J. G. Marin, Jesper B. Andersen, Domenico Alvaro, Alejandro Forner, Jesus M. Banales, Vincenzo Cardinale, Rocio I. R. Macias, Silve Vicent, Xin Chen, Chiara Braconi, Monique M. A. Verstegen, Laura Fouassier, Lewis Roberts, Alexander Scheiter, Florin M. Selaru, Katja Evert, Kirsten Utpatel, Laura Broutier, Massimiliano Cadamuro, Meritxell Huch, Robert Goldin, Sergio A. Gradilone, Yoshimasa Saito
Journal: Nature Reviews Gastroenterology & Hepatology (2023)
Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function
Authors: Ienglam Lei, Wei Huang, Pierre Emmanuel Noly, Suyash Naik, Miriyam Ghali, Liu Liu, Francis D. Pagani, Ashraf Abou El Ela, Jordan S. Pober, Bertram Pitt, Jeffrey L. Platt, Marilia Cascalho, Zhong Wang, Y. Eugene Chen, Richard M. Mortensen, Paul C. Tang
Journal: Science Translational Medicine (2023)

Preservation quality of donor hearts is a key determinant of transplant success. Preservation duration beyond 4 hours is associated with primary graft dysfunction (PGD). Given transport time constraints, geographical limitations exist for donor-recipient matching, leading to donor heart underutilization. Here, we showed that metabolic reprogramming through up-regulation of the enzyme immune response gene 1 (IRG1) and its product itaconate improved heart function after prolonged preservation. Irg1 transcript induction was achieved by adding the histone deacetylase (HDAC) inhibitor valproic acid (VPA) to a histidine-tryptophan-ketoglutarate solution used for donor heart preservation. VPA increased acetylated H3K27 occupancy at the IRG1 enhancer and IRG1 transcript expression in human donor hearts. IRG1 converts aconitate to itaconate, which has both anti-inflammatory and antioxidant properties. Accordingly, our studies showed that Irg1 transcript up-regulation by VPA treatment increased nuclear translocation of nuclear factor erythroid 2–related factor 2 (Nrf2) in mice, which was accompanied by increased antioxidant protein expression [hemeoxygenase 1 (HO1) and superoxide dismutase 1 (SOD1)]. Deletion of Irg1 in mice (Irg1 −/− ) negated the antioxidant and cardioprotective effects of VPA. Consistent with itaconate’s ability to inhibit succinate dehydrogenase, VPA treatment of human hearts increased itaconate availability and reduced succinate accumulation during preservation. VPA similarly increased IRG1 expression in pig donor hearts and improved its function in an ex vivo cardiac perfusion system both at the clinical 4-hour preservation threshold and at 10 hours. These results suggest that augmentation of cardioprotective immune-metabolomic pathways may be a promising therapeutic strategy for improving donor heart function in transplantation.